Correlation of HPV16 Gene Status and Gene Expression With Antibody Seropositivity and TIL Status in OPSCC.
antibody isotype
gene expression
human papillomavirus 16
immune response
oropharyngeal squamous cell carcinoma
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2020
2020
Historique:
received:
03
08
2020
accepted:
02
11
2020
entrez:
12
2
2021
pubmed:
13
2
2021
medline:
13
2
2021
Statut:
epublish
Résumé
Human papillomavirus 16 (HPV16) is the main cause of oropharyngeal squamous cell carcinoma (OPSCC). To date, the links between HPV16 gene expression and adaptive immune responses have not been investigated. We evaluated the correlation of HPV16 DNA, RNA transcripts and features of adaptive immune response by evaluating antibody isotypes against E2, E7 antigens and density of tumor-infiltrating lymphocytes (TIL). FFPE-tissue from 27/77 p16-positive OPSCC patients was available. DNA and RNA were extracted and quantified using qPCR for all HPV16 genes. The TIL status was assessed. Immune responses against E2 and E7 were quantified by ELISA (IgG, IgA, and IgM; 77 serum samples pre-treatment, 36 matched post-treatment). Amounts of HPV16 genes were highly correlated at DNA and RNA levels. RNA co-expression of all genes was detected in 37% (7/19). E7 qPCR results were correlated with higher anti-E7 antibody (IgG, IgA) level in the blood. Patients with high anti-E2 IgG antibody (>median) had better overall survival (p=0.0311); anti-E2 and anti-E7 IgA levels had no detectable effect. During the first 6 months after treatment, IgA but not IgG increased significantly, and >6 months both antibody classes declined over time. Patients with immune cell-rich tumors had higher levels of circulating antibodies against HPV antigens. We describe an HPV16 qPCR assay to quantify genomic and transcriptomic expression and correlate this with serum antibody levels against HPV16 oncoproteins. Understanding DNA/RNA expression, relationship to the antibody response in patients regarding treatment and outcome offers an attractive tool to improve patient care.
Identifiants
pubmed: 33575210
doi: 10.3389/fonc.2020.591063
pmc: PMC7871909
doi:
Types de publication
Journal Article
Langues
eng
Pagination
591063Informations de copyright
Copyright © 2021 von Witzleben, Currall, Wood, Chudley, Akinyegun, Thomas, Bendjama, Thomas, Friedmann, King, Laban and Ottensmeier.
Déclaration de conflit d'intérêts
Author KB was employed by company Transgene SA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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